“These data represent proof-of-concept that OPC-34712 may
be effective as adjunctive therapy in treating major depressive
disorder in patients with an inadequate response to ADT,”
said William H. Carson, M.D., President and CEO, OPDC.
“Importantly, these data allow us to advance to Phase 3
development for OPC-34712 with confidence.”

Trial results were presented at the American Psychiatric
Association's 2011 annual meeting. "Because many patients who
suffer from major depressive disorder do not respond adequately to
existing therapies, it's critical that we continue to investigate
new compounds as adjunctive therapy," said Study Investigator
Michael E. Thase, M.D., Professor of Psychiatry, University of
Pennsylvania School of Medicine. “The findings from this
study advance our knowledge about the utility of adjunctive agents
in patients who do not optimally respond to antidepressants
alone.”

OPC-34712 is a novel investigational psychotherapeutic compound
developed to provide improved efficacy and tolerability (e.g., less
akathisia, restlessness and/or insomnia) over established
adjunctive treatments for MDD. The compound has broad activity
across multiple monoamine systems and exhibits reduced partial
agonist activity at D2 dopamine receptors and enhanced affinity for
specific serotonin receptors (e.g., 5HT1a, 5HT2a and 5HT7).
OPC-34712 is currently poised to enter Phase 3 testing for
schizophrenia and adjunctive treatment of MDD and is in Phase 2
testing for adjunctive treatment of adult ADHD
Study Design and Findings

This Phase 2 multicenter, double-blind, placebo-controlled study
randomized 429 adult MDD patients who exhibited an inadequate
response to one to three ADTs in the current episode. The study was
designed to assess the efficacy and safety of OPC-34712 as an
adjunctive treatment to standard ADT. The ADTs included in the
study were desvenlafaxine, escitalopram, fluoxetine, paroxetine,
sertraline, and venlafaxine.

The study was comprised of three phases: I) a screening phase
(7–28 days) that identified patients who had not responded to
prior ADT within the current depressive episode; II) a prospective
8-week, single-blind phase to assess response status to ADT; and
III) a randomized phase of 6-week, double-blind assessment of
adjunctive OPC-34712 compared to placebo in patients who had an
inadequate response to ADT. Inadequate response to prospective ADT
was defined as less than 50% decrease in Hamilton Depression Rating
Score at the end of the 8-week single-blind phase. Patients were
randomized to daily OPC-34712 (0.15 mg, n=62; 0.50 ± 0.25
mg, n=120; or 1.5 ± 0.5 mg, n=121) or placebo (n=126)
adjunctive to ADT.

The primary efficacy endpoint was mean change in the MADRS total
score from baseline to Week 6 following randomization. Primary
analysis objectives were to compare the efficacy of the 0.5 mg/day
dose and the 1.5 mg/day dose of OPC-34712 with placebo.
Improvements in mean MADRS total score, from baseline to endpoint
as compared to placebo, were observed only for subjects receiving
adjunctive OPC 34712 at the 1.5 mg/day dose compared with placebo
(p=0.0303); improvements in MADRS total score for subjects
receiving the 0.5 mg/day dose were not different compared with
placebo (p>0.05).

Major depressive disorder (MDD) is characterized by one or more
major depressive episodes, (i.e., at least two weeks of depressed
mood or loss of interest accompanied by at least four additional
symptoms of depression). MDD affects approximately 14.2 million
American adults in a given year, and today it is often treated with
antidepressants (1); however, in many cases patients fail to
respond adequately to treatment (2). Depression is one of the
leading causes of disability in the U.S. In 2000, the total
economic burden of treating depression in the U.S. was $83.1
billion, with workplace costs, including missed days and lack of
productivity due to illness, accounting for the majority of the
total economic burden (62 percent). Other economic burdens in 2000
included $26.1 billion (31 percent) for treatment costs and $5.4
billion (7 percent) for suicide-related costs (3).